In the last three years, prolonged extracorporeal circulation (ECC) for cardiopulmonary support has become a clinical reality. During these years our laboratory, supported by grants from the NHLI, has contributed to the understanding of normal physiologic, hematologic, and biochemical responses to ECC which we hopse has aided in the smooth transition from orderly laboratory investigation to successful clinical application with minimal risk. With clinical application has come better understanding of device design and coagulation control, and recognition of new problems related to host defenses and patient selection. Propert patient selection and evaluation of the effectiveness of extracorporeal support is being evaluated by NHLI in a clinical combined collaborative study supported by a research contract. Our laboratory is fortunate to be one of the 9 contractors in that study. With the collaborative clinical study underway, it becomes even more important to pursue laboratory study of prolonged ECC to solve the clinical problems of progressive lung damage, coagulation and anticoagulation, and sepsis. This proposal outlines our plans for continuing laboratory research emphasizing two major, interrelated programs: (1) coagulation/anticoagulation and platelet mechanisms, and (2) physiology and pathophysiology and ECMO support. Subdivisions of these programs interrelate at several levels and should provide a suitable testing ground for answering the questions raised in clinical studied. BIBLIOGRAPHIC REFERENCES: Bartlett, R.H., Cazzaniga, A.B., Jefferies, R., Huxtable, R.F., Haiduc, N., Fong, S.W.: Extracorporeal Membrane Oxygenation (ECMO) Cardiopulmonary Support in Infancy. Trans. Am. Soc. Artif. Intern. Organs 22:80, 1976. Roohk, H.V., Pick, J., Hill, R., Hung, E., Bartlett, R.H.: Kintetics of Fibrinogen and Platelet Adherence to Biomaterials. Trans. Am. Soc. Artif. Intern. Organs 22:1, 1976.